The overall objective of the proposed work is to identify and characterize mechanisms resonsible for the intestinal transport of bile acids. Recent studies have involved two steps in the sequential breakdown of the small intestine from in vivo exeriments to progressively smaller cellular and subcellular fractions that are more intimately involved in bile acid transport. First, the transport of glycocholate was studied in epithelial cells isolated from rat ileum. The rate of uptake of this bile acid was correlated with (Na ion plus K ion)-ATPase activity in the isolated cells. The concentration of ouabain necessary to produce one-half maximal inhibition of glycocholate uptake and (Na ion plus K ion)-ATPase activity was similar at 10-5M. Second, the transport of another bile acid, glycodeoxycholate, was studied in vesicles derived from rat jejunal and ileal brush border membranes. In ileal, but not jejuanal, vesicles the bile acid uptake showed a transient vesicle/medium ratio greater than 1 in the presence of an initial sodium gradient. The vesicle system reflected kinetics and characteristics of bile acid transport previously seen in intact intestinal preparations and catalyzed the co-transport of Na ion and bile acid across the ileal membrane in a manner analogous to D-glucose transport. These and other observations suggest that the active ileal transport of bile acid may be a specific effect of the Na ion electrochemical gradient. The movement of sodium from the lumen into the cell down its concentration gradient provides the free energy to drive bile acid against its concentration gradient. The low intracellular sodium concentration necessary for continued operation of the system is maintained by the active extrusion of the cation across the basolateral membranes with energy derived from ATP hydrolysis by ouabain sensitive (Na ion plus K ion)-ATPase.